{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:46:55Z","timestamp":1779151615130,"version":"3.51.4"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,9,4]]},"abstract":"\n Background<\/jats:title>\n \n Preclinical data have indicated a link between use of vitamin K antagonists (\n VKA<\/jats:styled-content>\n ) and detrimental effects on vascular structure and function. The objective of the present study was to determine the relationship between\n VKA<\/jats:styled-content>\n intake and different phenotypes of subclinical cardiovascular disease in the population.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Clinical and laboratory data, as well as medical\u2013technical examinations were assessed from 15\u00a0010 individuals aged 35 to 74\u00a0years during a highly standardized 5\u2010hour visit at the study center of the population\u2010based Gutenberg Health Study. In total, the study sample comprised 287\n VKA<\/jats:styled-content>\n users and 14\u00a0564\n VKA<\/jats:styled-content>\n nonusers. Multivariable analysis revealed an independent association between\n VKA<\/jats:styled-content>\n intake and stiffness index (\u03b2=+2.54\u00a0m\/s; [0.41\/4.66];\n P<\/jats:italic>\n =0.019), ankle\u2010brachial index (\u03b2=\u22120.03; [\u22120.04\/\u22120.01];\n P<\/jats:italic>\n <0.0001), intima\u2010media thickness (\u03b2=+0.03\u00a0mm [0.01\/0.05];\n P<\/jats:italic>\n =0.0098), left ventricular ejection fraction (\u03b2=\u22124.02% [\u22124.70\/\u22123.33];\n P<\/jats:italic>\n <0.0001), E\/E\u2032 (\u03b2=+0.04 [0.01\/0.08];\n P<\/jats:italic>\n =0.014) left ventricular mass (\u03b2=+5.34\u00a0g\/m\n 2.7<\/jats:sup>\n [4.26\/6.44];\n P<\/jats:italic>\n <0.0001), and humoral markers of cardiac function and inflammation (midregional pro\u2010atrial natriuretic peptide: \u03b2=+0.58\u00a0pmol\/L [0.50\/0.65];\n P<\/jats:italic>\n <0.0001; midregional pro\u2010adrenomedullin: \u03b2=+0.18\u00a0nmol\/L [0.14\/0.22];\n P<\/jats:italic>\n <0.0001; N\u2010terminal pro B\u2010type natriuretic peptide: \u03b2=+1.90\u00a0pg\/mL [1.63\/2.17];\n P<\/jats:italic>\n <0.0001; fibrinogen: \u03b2=+143\u00a0mg\/dL [132\/153];\n P<\/jats:italic>\n <0.0001; C\u2010reactive protein: \u03b2=+0.31\u00a0mg\/L [0.20\/0.43];\n P<\/jats:italic>\n <0.0001). Sensitivity analysis in the subsample of participants with atrial fibrillation stratified by intake of\n VKA<\/jats:styled-content>\n demonstrated consistent and robust results. Genetic variants in\n \n CYP<\/jats:styled-content>\n 2C9\n <\/jats:italic>\n ,\n \n CYP<\/jats:styled-content>\n 4F2\n <\/jats:italic>\n , and\n \n VKORC<\/jats:styled-content>\n 1\n <\/jats:italic>\n were modulating effects of\n VKA<\/jats:styled-content>\n on subclinical markers of cardiovascular disease.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These data demonstrate negative effects of\n VKA<\/jats:styled-content>\n on vascular and cardiac phenotypes of subclinical cardiovascular disease, indicating a possible influence on long\u2010term disease development. These findings may be clinically relevant for the provision of individually tailored antithrombotic therapy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.008650","type":"journal-article","created":{"date-parts":[[2018,9,17]],"date-time":"2018-09-17T18:20:49Z","timestamp":1537208449000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population\u2010Based Gutenberg Health Study"],"prefix":"10.1161","volume":"7","author":[{"given":"Lisa","family":"Eggebrecht","sequence":"first","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine Center for Cardiology University Medical Center Mainz Mainz Germany"},{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen H.","family":"Prochaska","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine Center for Cardiology University Medical Center Mainz Mainz Germany"},{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"},{"name":"Center for Thrombosis and Hemostasis University Medical Center Mainz Mainz Germany"},{"name":"DZHK (German Center for Cardiovascular Research) Partner Site Rhine\u2010Main Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Schulz","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine Center for Cardiology University Medical Center Mainz Mainz Germany"},{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Arnold","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine Center for Cardiology University Medical Center Mainz Mainz Germany"},{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus","family":"J\u00fcnger","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine Center for Cardiology University Medical Center Mainz Mainz Germany"},{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"G\u00f6bel","sequence":"additional","affiliation":[{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"},{"name":"DZHK (German Center for Cardiovascular Research) Partner Site Rhine\u2010Main Mainz Germany"},{"name":"Center for Cardiology \u2013 Cardiology I University Medical Center Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmar","family":"Laubert\u2010Reh","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine Center for Cardiology University Medical Center Mainz Mainz Germany"},{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Binder","sequence":"additional","affiliation":[{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"},{"name":"Institute for Medical Biometry and Statistics University of Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred E.","family":"Beutel","sequence":"additional","affiliation":[{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"},{"name":"Department of Psychosomatic Medicine and Psychotherapy University Medical Center Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobert","family":"Pfeiffer","sequence":"additional","affiliation":[{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"},{"name":"Department of Ophthalmology University Medical Center Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Blankenberg","sequence":"additional","affiliation":[{"name":"Clinic for General and Interventional Cardiology University Heart Centre Hamburg Hamburg Germany"},{"name":"DZHK (German Center for Cardiovascular Research) Partner Site Hamburg\/Kiel\/L\u00fcbeck Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl J.","family":"Lackner","sequence":"additional","affiliation":[{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"},{"name":"DZHK (German Center for Cardiovascular Research) Partner Site Rhine\u2010Main Mainz Germany"},{"name":"Institute for Clinical Chemistry and Laboratory Medicine University Medical Center Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henri M.","family":"Spronk","sequence":"additional","affiliation":[{"name":"Laboratory for Clinical Thrombosis and Hemostasis Department of Internal Medicine Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo","family":"ten Cate","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Hemostasis University Medical Center Mainz Mainz Germany"},{"name":"Laboratory for Clinical Thrombosis and Hemostasis Department of Internal Medicine Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"M\u00fcnzel","sequence":"additional","affiliation":[{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"},{"name":"DZHK (German Center for Cardiovascular Research) Partner Site Rhine\u2010Main Mainz Germany"},{"name":"Center for Cardiology \u2013 Cardiology I University Medical Center Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp S.","family":"Wild","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine Center for Cardiology University Medical Center Mainz Mainz Germany"},{"name":"Center for Translational Vascular Biology (CTVB) University Medical Center Mainz Mainz Germany"},{"name":"Center for Thrombosis and Hemostasis University Medical Center Mainz Mainz Germany"},{"name":"DZHK (German Center for Cardiovascular Research) Partner Site Rhine\u2010Main 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